St. John's Wort
Stephen Barrett, M.D.
St. John's wort (Hypericum perforatum) has been widely claimed to be
effective as an antidepressant. The mechanism of action is unknown; and
the active ingredient, if any, has not been ascertained . Studies of
extracts standardized for hypericin (one of the herb's constituents)
have found it to be about twice as effective as a placebo. A few studies
have found it somewhat more effective than a standard antidepressant.
However, none of these studies lasted more than six weeks, which is not
long enough to determine how long the herb would be effective or to
detect any long-term adverse effects . In addition, some of the
studies were not well-designed [3,4]. In most of these studies, the
diagnosis was not well established, the placebo response rate was lower
than usually seen in such studies, the dosage of standard
antidepressants was low, and the dosage of hypericin varied more than
six-fold. . No serious side effects were reported, but minor side
effects include gastrointestinal discomfort, fatigue, dry mouth,
dizziness, skin rash, and hypersensitivity to sunlight. However, in
February 2000, British journal Lancet carried reports that St.
John's wort could interfere with the effectiveness of an AIDS remedy (indinavir)
; an immunosuppressive drug (cyclosporin) used to protect patients
after heart transplantation ; and an anticoagulant (warfarin) .
Based on this study and other reports in the medical literature, the FDA
issued a Public Health Advisory stating:
St. John's wort appears to be an inducer of an important metabolic
pathway, cytochrome P450. As many prescription drugs used to treat
conditions such as heart disease, depression, seizures, certain
cancers or to prevent conditions such as transplant rejection or
pregnancy (oral contraceptives) are metabolized via this pathway,
health care providers should alert patients about these potential drug
interactions to prevent loss of therapeutic effect of any drug
metabolized via the cytochrome P450 pathway .
St. John's wort should not be used by women who are pregnant or are
breastfeeding. Nor should it be used together with standard
antidepressants. The potency and purity of the preparations sold in the
United States are unknown .
There is no published evidence that St. John's wort is effective
against severe depression, which, in any case, should receive
professional help. For mild depression, psychotherapy directed at
resolving the cause of the depression might be more prudent.
The NIH Office of Alternative Medicine has funded a 3-year,
clinical trial that will compare the effects of hypericum, a
placebo, and a standard antidepressive drug on patients who are followed
for up to six months . The results are expected in the year 2002.
Regardless of the outcome, however, another problem must be overcome
before consumers could use St. John's wort effectively. A Good
Housekeeping Institute analysis of six widely available St. John's wort
supplement capsules and four liquid extracts revealed a lack of
consistency of the suspected active ingredients, hypericin and
pseudohypericin. The study found:
- A 17-fold difference between the capsules containing the smallest
amount of hypericin and those containing the largest amount, based on
manufacturer's maximum recommended dosage.
- A 13-fold difference in pseudohypericin in the capsules.
- A 7-to-8-fold differential from the highest to the lowest levels
of liquid extracts .
A sinilar investigation by the Los Angeles Times found that 7
of10 products contained between 75% and 135% of the labeled hypericin
level, and three contained no more than about half the labeled potency
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St. John's wort for depression -- an overview and meta-analysis of
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St. John's wort as an antidepressant: Longer term studies are needed
before it can be recommended in major depression. British Medical
Journal 313:241-242, 1996.
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St. John's wort in depression. Archives of Internal Medicine
- Piscitelli SC and others.
Indinavir concentrations and St John's wort. Lancet 355:547, 2000.
- Ruschitzka F and others.
Acute heart transplant rejection due to Saint John's wort. Lancet
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drug interactions with St. John's wort and indinavir and other drugs.
FDA Health Advisory, Feb 10, 2000.
- St. John's wort study launched. Complementary and Alternative
Medicine at the NIH 4(4):5, October 1997.
- Good Housekeeping Institute. New Good Housekeeping Institute study
finds drastic discrepancy in potencies of popular herbal supplement.
News release, Consumer Safety Symposium on Dietary Supplements and
Herbs, New York City, March 3, 1998.
- Monmaney T. Labels' potency claims often inaccurate, analysis
finds. Spot check of products finds widely varying levels of key
ingredient. But some firms object to testing method and defend their
brands' quality. Los Angeles Times, Aug 31, 1998.